Wyo. flock to be killed, tested after scrapie foundBy The Associated Press

CHEYENNE - Somewhere near Moorcroft, in an unincorporated area of northeastern Wyoming, a livestock owner will hand over his entire flock of sheep next week to the federal government for a mass execution. The rancher knows what will happen: his herd of roughly 300 sheep will be transported live out of state and taken to a slaughter plant where they will be euthanized, their brains and lymph node tissue harvested for testing.

He'll lose his herd because he owned the first U.S. sheep to test positive for a rare strain of scrapie _ a disease found in sheep and goats that's similar to mad cow disease in cattle and chronic wasting disease in sheep and elk.

Still, state statute prohibits officials from releasing the rancher's identity, and attempts by The Associated Press to reach him were unsuccessful.

Scrapie itself is rare in the United States. Out of more than 115,000 animals tested since 2003, only 300 have tested positive; federal officials hope to eliminate scrapie from U.S. herds by the end of 2010.

But the Wyoming rancher's case is even more rare: Fewer than 300 cases worldwide have been recorded of the "Nor98-like" strain of scrapie, so-named because it was first diagnosed in Norway in 1998.

"This is very unusual," Larry Cooper, regional spokesman in Fort Collins, Colo., for Animal Plant Health Inspection Service, or APHIS, said of the first discovery of a Nor98-like strain of scrapie in the U.S.

"It doesn't indicate that we're going to have mass outbreaks of this particular strain, it just indicates that one of these animals from Europe ended up in our system."

There are no known human health risks associated with scrapie. Cooper and Bryce Reece, executive vice president of the Wyoming Wool Growers Association, say consumers and livestock owners have nothing to fear from the diagnosis.

"From an industry standpoint, we're not at all concerned or alarmed by it," Reece said. "It's more of an interest to the researchers or the scientists than it is to the industry. I'm sure they're all questioning themselves as to how it got here."

Dr. Mark Hall, head of the special pathology section of the National Veterinary Services Laboratories in Ames, Iowa, agreed.

"It is something of interest and something I think we want to continue to look at," Hall said. "But this is certainly not a shocking revelation or anything like that. At this point, I don't think there's any evidence that there's any great need for concern."

"It means our surveillance system is working," Dr. Diane Sutton, National Scrapie Program coordinator, said. "We found it utilizing our current technologies to find scrapie cases in the United States."

APHIS notified the state last month that the sheep rancher's ewe tested positive for a form of scrapie consistent with the Nor98 strain. The ewe was slaughtered in Michigan last fall as part of the USDA's regular scrapie slaughter surveillance program and traced back to the Wyoming flock.

Dr. Walt Cook, acting state veterinarian, said the government would pay the livestock owner an indemnity fee based on fair market value for the sheep, before "depopulating" the herd.

"It's the best and the simplest thing to do," Cook said. "It's unfortunate to put down all those sheep, but it will allow us to test them and make sure no other animals are infected."

Cook and Sutton said the infected ewe's owner had one other option: to quarantine his flock, during which time he couldn't sell breeding animals for several years while the flock was monitored to ensure no other cases of the disease appeared.

"Economically it doesn't make much difference one way or the other," Cook said of the rancher's options. "Obviously, by depopulating, he has to go through the loss of his animals, which can be distressful."

Reece said when traditional scrapie is found in a flock, typically up to 10 percent of the rest of that herd can be infected with the disease. But with Nor98, when one case is found, to date it has been the only one found in the flock.

"I would bet we're not gonna see another one of these in Wyoming, and maybe not even in the United States, but who knows?" Reece said. "With 300 cases worldwide, it's not something out there that's highly transmittable."

He said that if an animal becomes infected with scrapie, it will die from it: "It's 100 percent fatal, and because it's 100 percent fatal it's a self-limiting disease."

"From a practical standpoint, scrapie is nothing," Reece said. "Pneumonia probably kills more sheep than anything else out there, but because of scrapie's similarities to mad cow disease, from a marketing and consumer standpoint it is important for the U.S. to eradicate the disease from the U.S."

Cooper said the effects of Nor98 are basically the same as those seen in classic scrapie _ the disease attacks the central nervous system of infected animals, causing behavioral changes such as tremors of the head and neck.

Classical scrapie is believed to be primarily transmitted through exposure to placenta and birth fluids from infected animals or from facilities in which infected animals have lambed.

The lamb and wool production business is a $50 million-a-year industry in Wyoming, according to Reece, and a $500 million-a-year industry nationally. According to Cooper, many sheep-importing countries require that the U.S. be free of scrapie for seven years before they'll import U.S. breeding sheep.

CHEYENNE, Wyo. - On Friday, March 16, 2007, the Wyoming Livestock Board (WLSB) was notified by officials of the USDA Animal Plant Health Inspection Service (APHIS) that an adult female sheep had tested positive for a form of scrapie consistent with the Nor98 strain. The ewe was slaughtered in Michigan, where it was tested as part of USDA’s regulatory scrapie slaughter surveillance program and traced back to a flock in Wyoming. The results of this case are distinctly different from those seen for bovine spongiform encephalopathy (BSE) or classical scrapie.

Scrapie is a transmissible spongiform encephalopathy and falls into the same category of diseases as chronic wasting disease, found in deer and elk, and bovine spongiform encephalopathy, found in cattle. The disease is limited to sheep and goats and takes years to affect an animal after it has been infected. Scrapie causes sheep to itch and scratch (scrape) wool off, change their behavior and lose body condition; it ultimately ends in death.

Nor98-like scrapie differs from classical scrapie in the distribution of brain lesions and in the course of disease progression and epidemiology. Some sheep that are genetically resistant to the classic form of the disease may be susceptible to the Nor98-like strain. Oddly, Nor98-like scrapie is usually diagnosed during surveillance in animals without clinical signs. There are no known human health risks associated with either form of scrapie.

This is the first time a Nor98-like strain of scrapie has been documented in the United States. It gets the "Nor98-like" name because it is similar to a case first diagnosed in Norway in 1998. This strain of scrapie is a rare disease even in Europe. Since 1998, fewer than 300 cases have been diagnosed in all of Europe. It is usually seen in single animals and does not tend to become widespread in a flock. In contrast, in flocks infected by classical scrapie typically more than 10 percent of the genetically susceptible animals test positive.

"This provides evidence that the surveillance program is working," said Bryce Reece, executive director of the Wyoming Wool Growers Association. "It also indicates that the program is on the cutting-edge of science to detect such a rare disease during standard surveillance."

The Wyoming Livestock Board does not expect the Nor98-like strain of scrapie to become a major disease problem for the sheep industry in Wyoming. Risk is limited because diagnosis of Nor98-like scrapie is usually an incidental event, with even highly-exposed flock mates of the positive animal normally unaffected.

The infected ewe lambed in it in what is considered a low-risk, range-lambing environment. Nonetheless, the WLSB, APHIS and the Wyoming Wool Growers Association plan to assertively pursue this case to make sure that this strain of scrapie is extinguished and does not establish itself in the U.S.

The agencies continue to encourage producers to monitor their sheep for signs of scrapie and other diseases, and to notify their veterinarian if they discover anything unusual.

The positive ewe was purchased as an adult within the last several years and moved to a Wyoming flock near the Black Hills. The producer was notified and his flock quarantined as a precautionary measure. An epidemiologic investigation is ongoing and the producer has been cooperative. The case fits the pattern found in Europe - a single, older sheep that was not exhibiting clinical signs of scrapie.

The regulatory scrapie slaughter surveillance program is a targeted slaughter surveillance program for sheep and goats designed to identify infected animals and flocks. USDA is conducting this surveillance as part of a program to eradicate scrapie from the United States by the end of 2010. Reece said that the sheep industry supports this program and is committed to eliminating scrapie from the United States.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

12/10/76AGRICULTURAL RESEARCH COUNCILREPORT OF THE ADVISORY COMMITTE ON SCRAPIEOffice NoteCHAIRMAN: PROFESSOR PETER WILDY

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A The Present Position with respect to ScrapieA] The Problem

Scrapie is a natural disease of sheep and goats. It is a slowand inexorably progressive degenerative disorder of the nervous systemand it ia fatal. It is enzootic in the United Kingdom but not in allcountries.

The field problem has been reviewed by a MAFF working group(ARC 35/77). It is difficult to assess the incidence in Britain fora variety of reasons but the disease causes serious financial loss;it is estimated that it cost Swaledale breeders alone $l.7 M duringthe five years 1971-1975. A further inestimable loss arises from theclosure of certain export markets, in particular those of the UnitedStates, to British sheep.

It is clear that scrapie in sheep is important commercially andfor that reason alone effective measures to control it should bedevised as quickly as possible.

Recently the question has again been brought up as to whetherscrapie is transmissible to man. This has followed reports that thedisease has been transmitted to primates. One particularly luridspeculation (Gajdusek 1977) conjectures that the agents of scrapie,kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy ofmink are varieties of a single "virus". The U.S. Department ofAgriculture concluded that it could "no longer justify or permitscrapie-blood line and scrapie-exposed sheep and goats to be processedfor human or animal food at slaughter or rendering plants" (ARC 84/77)"The problem is emphasised by the finding that some strains of scrapieproduce lesions identical to the once which characterise the humandementias"

Whether true or not. the hypothesis that these agents might betransmissible to man raises two considerations. First, the safetyof laboratory personnel requires prompt attention. Second, actionsuch as the "scorched meat" policy of USDA makes the solution of theacrapie problem urgent if the sheep industry is not to suffergrievously.

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76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

Like lambs to the slaughter31 March 2001Debora MacKenzieMagazine issue 2284What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...

Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.

Chronic wasting disease (CWD) is a transmissiblespongiform encephalopathy (TSE) of deer and elk,and little is known about its transmissibility to otherspecies. An important factor controllinginterspecies TSE susceptibility is prion protein (PrP)homology between the source and recipientspecies/genotypes. Furthermore, the efficiency with whichthe protease-resistant PrP (PrP-res) of onespecies induces the in vitro conversion of the normal PrP(PrP-sen) of another species to theprotease-resistant state correlates with the cross-speciestransmissibility of TSE agents. Here weshow that the CWD-associated PrP-res (PrPCWD) of cervidsreadily induces the conversion of recombinant cervid PrP-senmolecules to the protease-resistant state in accordancewith the known transmissibility of CWD between cervids. In contrast,PrPCWD-induced conversions of human and bovine PrP-sen weremuch less efficient, and conversion of ovine PrP-sen wasintermediate. These results demonstrate a barrier at themolecular level that should limit the susceptibility of these non-cervidspecies to CWD.

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Clearly, it is premature to draw firm conclusions about CWDpassing naturally into humans, cattle and sheep, but the presentresults suggest that CWD transmissions to humans would be aslimited by PrP incompatibility as transmissions of BSE or sheepscrapie to humans. Although there is no evidence that sheepscrapie has affected humans, it is likely that BSE has caused variantCJD in 74 people (definite and probable variant CJD cases todate according to the UK CJD Surveillance Unit). Given thepresumably large number of people exposed to BSE infectivity,the susceptibility of humans may still be very low compared withcattle, which would be consistent with the relatively inefficientconversion of human PrP-sen by PrPBSE. Nonetheless, sincehumans have apparently been infected by BSE, it would seem prudentto take reasonable measures to limit exposure of humans(as well as sheep and cattle) to CWD infectivity as has beenrecommended for other animal TSEs.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease ofsheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) thatwere exposed to the infectious agents only by their nonforced consumption ofknown infectious tissues. The asymptomatic incubation period in the onemonkey exposed to the virus of kuru was 36 months; that in the two monkeysexposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months,respectively; and that in the two monkeys exposed to the virus of scrapiewas 25 and 32 months, respectively. Careful physical examination of thebuccal cavities of all of the monkeys failed to reveal signs or orallesions. One additional monkey similarly exposed to kuru has remainedasymptomatic during the 39 months that it has been under observation.

Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically byhuman pituitary growth hormone, corneal transplants, and dura mater grafts(1). Possible accidental transmission has been reported in only fourpeople-a neurosurgeon (2), a pathologist (3), and two laboratory technicians(4,5) . We have encountered an unusually rapid case of CJD probably acquiredthrough handling of sheep and human dura mater.In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia ofthe left arm. A few days later he had spatial disorientation, apraxia, andgait ataxia. In June he was admitted and a neurologist suspected CJD on thebasis of the clinical signs, typical electroencephalogram (EEG) pattern, andhistory. An EEG in June revealed a typical pattern of periodic biphasic andtriphasic sharp wave complexes. We saw the patient in July, 1992. He wasawake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxiamainly of the left side, rigidity of wrists, spasticity of all muscles,myoclonus of the left arm, increased tendon reflexes, ataxia of limbs andtrunk, and incoordination of left arm. Within 3 weeks he had impairedconsciousness and attention, mildly impaired memory, and threatening visualhallucinations with restless turning. He had periodic states with movementsof his head and eye-bulbs resembling tonic adversive seizures. During sleepthese motor disturbances stopped. 2 1/2 months later the patient died.

This patient had worked with sheep and human dura mater from 1968 to 1972.He handled about 150 specimens of ovine origin and at least a dozen humanpreparations for research. Handling involved opening skulls with a band saw,removing dura, and testing them either fresh (usually), preserved, orlyophilised for mechanical qualities. These specimens were sent to a companythat has sold dura mater preparations by which CJD was transmitted in sixinstances. No information was available from the company about a possibleconnection with this patient's disease and the earlier cases of transmittedCJD. Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluidobtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL,compared with 16.7 ng/mL in serum of other cases (6). Proton magneticresonance spectroscopy of parieto-occipital and temporal grey matter,parietal white matter, and thalamus revealed a 20-30% reduction ofN-acetylaspartate, as described (7). DNA was genotyped with allele-specificoligonucleotides (8) and was homozygous for methionine at the polymorphiccodon 129. Subsequent direct DNA sequencing for the PrP gene open-readingframe demonstrated normal sequence on both alleles, excluding known or novelpathogenic PrP mutations.

It is tempting to speculate that prions were transmitted to this patientfrom sheep or human dura mater through small lacerations of his skin, butthe patient and his wife did not remember any significant injury during hisfour years of working with these samples. It cannot be excluded that thiswas a case of sporadic CJD although this assumption is unlikely in view ofthe clinical course which was similar to iatrogenic CJD transmitted byperipheral inoculation, such as with human pituitary growth hormone orgonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebralinoculation with the transmissible agent, for instance following dura matergrafts (2-5), present with a dementing picture, as is usual in sporadic CJD,rather than with ataxia as in this case.

18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7December 2006 are now available.

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64. A member noted that at the recent Neuroprion meeting, a study waspresented showing that in transgenic mice BSE passaged in sheep may be morevirulent and infectious to a wider range of species than bovine derived BSE.

Other work presented suggested that BSE and bovine amyloidotic spongiformencephalopathy (BASE) MAY BE RELATED. A mutation had been identified in theprion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO AMUTATION FOUND IN CASES OF SPORADIC CJD.

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE straindiscovered recently in Italy, and similar or different atypical BSE caseswere also reported in other countries. The infectivity and phenotypes ofthese atypical BSE strains in humans are unknown. In collaboration withPierluigi Gambetti, as well as Maria Caramelli and her co-workers, we haveinoculated transgenic mice expressing human prion protein with brainhomogenates from BASE or BSE infected cattle. Our data shows that about halfof the BASE-inoculated mice became infected with an average incubation timeof about 19 months; in contrast, none of the BSE-inoculated mice appear tobe infected after more than 2 years.

***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent thanclassical BSE in humans.***